title: Antiparasitic hybrids of Cinchona alkaloids and bile acids.
abstract: A series of 16 hybrids of Cinchona alkaloids and bile acids (4a-h, 5a-h) was prepared by means of a Barton-Zard decarboxylation reaction. Quinine, quinidine, cinchonine and cinchonidine were functionalized at position C-2 of the quinoline nucleus by radical attack of a norcholane substituent. The newly synthesized hybrids were evaluated in vitro for their antitrypanosomal, antileishmanial and antiplasmodial activities, along with their cytotoxicity against WI38, a normal human fibroblast cell line. Seven compounds (4d, 4f, 4h, 5b, 5d, 5f, 5h) showed promising trypanocidal activity with IC₅₀ values in the same range as the commercial drug suramine. Moreover all the 16 hybrids showed antiplasmodial activity (IC₅₀ ≤ 6 μg/ml), particularly those containing a nor-chenodeoxycholane moiety (4b, 4d, 4f, 4h, 5b, 5d, 5f, 5h) with IC₅₀ values comparable to those of the natural alkaloids, and selectivity indices in the range of 5.6-15.7.
authors.affiliation: UMYMFOR, Departamento de Química Orgánica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria, Pab. 2, 1428 Buenos Aires, Argentina.
authors.forename: Aurélie
authors.initials: A
authors.lastname: Leverrier
authors.forename: Joanne
authors.initials: J
authors.lastname: Bero
authors.forename: Michel
authors.initials: M
authors.lastname: Frédérich
authors.forename: Joëlle
authors.initials: J
authors.lastname: Quetin-Leclercq
authors.forename: Jorge
authors.initials: J
authors.lastname: Palermo
mesh_terms: D000977:Antiparasitic Agents / Q000737:chemistry* / Q000494:pharmacology* / Q000633:toxicity; D001647:Bile Acids and Salts / Q000737:chemistry*; D002460:Cell Line; D002930:Cinchona Alkaloids / Q000737:chemistry* / Q000494:pharmacology* / Q000633:toxicity; D006801:Humans; D020128:Inhibitory Concentration 50
chemical_list: D000977:Antiparasitic Agents; D001647:Bile Acids and Salts; D002930:Cinchona Alkaloids
keywords: Antiparasitic activity; Barton–Zard reaction; Bile acids; Cinchona alkaloids; Hybrids